Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1 Journal Article


Authors: Prabakaran, T.; Bodda, C.; Krapp, C.; Zhang, B. C.; Christensen, M. H.; Sun, C.; Reinert, L.; Cai, Y.; Jensen, S. B.; Skouboe, M. K.; Nyengaard, J. R.; Thompson, C. B.; Lebbink, R. J.; Sen, G. C.; van Loo, G.; Nielsen, R.; Komatsu, M.; Nejsum, L. N.; Jakobsen, M. R.; Gyrd-Hansen, M.; Paludan, S. R.
Article Title: Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1
Abstract: Negative regulation of immune pathways is essential to achieve resolution of immune responses and to avoid excess inflammation. DNA stimulates type I IFN expression through the DNA sensor cGAS, the second messenger cGAMP, and the adaptor molecule STING. Here, we report that STING degradation following activation of the pathway occurs through autophagy and is mediated by p62/SQSTM1, which is phosphorylated by TBK1 to direct ubiquitinated STING to autophagosomes. Degradation of STING was impaired in p62-deficient cells, which responded with elevated IFN production to foreign DNA and DNA pathogens. In the absence of p62, STING failed to traffic to autophagy-associated vesicles. Thus, DNA sensing induces the cGAS-STING pathway to activate TBK1, which phosphorylates IRF3 to induce IFN expression, but also phosphorylates p62 to stimulate STING degradation and attenuation of the response. © 2018 The Authors
Keywords: innate immunity; autophagy; p62/sqstm1; dna sensing; sting
Journal Title: EMBO Journal
Volume: 37
Issue: 8
ISSN: 0261-4189
Publisher: Wiley Blackwell  
Date Published: 2018-04-13
Start Page: e97858
Language: English
DOI: 10.15252/embj.201797858
PROVIDER: scopus
PMCID: PMC5897779
PUBMED: 29496741
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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  1. Craig Bernie Thompson
    140 Thompson